Ipratropium, is a derivative of N-isopropil noratropine, with anticholinergic effects in the upper respiratory tract. The basic patent is U.S. Pat. No. 3,505,337. For symptomatic treatment of the rhinorrhea associated with perennial rhinitis, a nasal spray (Atrovent®) is available in the market.
Oxymetazoline is an imidazol-simpathetic vasoconstrictor preferably used locally intranasal to unblock nasal mucous membrane. The basic patent of oximetazoline is DE 1117588 (Merck® lliadin, metered dose aerosol, drops, pediatric aerosol) is available in the market. There is an aerosol containing Ipratropium and Xilometazoline, a similar molecule, available the market (Otrivin Com®) It has been described a combination of oxyrnetazoline or a derivative of its salt, with ipratropium or a derivative of its salt for the treatment of symptoms of common cold and/or rhinitis and related symptoms such as nasal congestion, sneezing and hypersecretion (WO 2014158119 A1) which is not actually in the market, with the following composition:
IngredientsQuantityIpratropium0.005%-0.5% weight/Volume(0.05Bromidemg/ml-5 mgs/ml)Oximetazoline0.005%-0.5% weight/Volume(0.05hydrochloridemg/ml-5 mgs/ml)EDTA disodium0.005%-0.1% weight/volumenGlycerol0%-30.0% weight/volumenBenzalconium0%-0.02 weight/volumenChlorateBuffer (pH adjust)u.s.Wateru.s.
There is a previous patent number 247216 with International Publication WO 03/024433 A2 which comprises the combination of ipratropium bromide and Xilometazolina for symptoms associated with common cold based on nasal congestion, sneezing and hypersecretion, caused by viral infections, allergic or perennial rhinitis.
However, a preparation comprising oxymetazoline salt or derivative, in combination with ipratropium bromide salt or derivative, intranasally used, specifically for relief of cough caused by increased discharge runny nose, towards the retro-nasopharynx, or also called, postnasal drip syndrome has not been described and is not currently available in the market.
The oxymetazoline hydrochloride is a sympathetic agent that shrinks arterioles network within nasal mucosa producing long decongestive and antisecretor effects, therefore it has been used in common cold, to permeate nostrils and decrease rhinorrhea (synonym: catarrh, coryza, nasopharyngitis, cold or flu).
Oxymetazoline dilutions used 0.01 for babies of 6 months to two years of age, 0.25% for children aged 2 to 12 years old and 0.50% ai for children and adults aged 12 years or older.
Ipratropium Bromide is an anticolinergic agent that antagonizes the action of acetylcholine released by nerve endings. Nasal hypersecretion associated to common cold and other upper respiratory tract infections involves neurogenic reflexes with release of acetylcholine at the nasosinusal mucosa level. These reflexes are antagonized by atropine and ipratropium bromide (both are anticolinergic, with anti-acetylcholine effect). This has been proven by studies in which nasal fluid was measured in individuals with naturally acquired common cold1-3.
At the present time, approaches to the use of oxymetazoline and Ipratropium, are:                For oxymetazoline hydrochloride, because its permeate effect of nose due to reduce congestion of the nasal mucosal superficial vessels (decongestant effect), with concomitant decrease volume occupied by these tissues (particularly the turbinate erectil tissue), increasing the nostrils light, which allows more space for air passage when they are blockade during a common cold, nasopharyngitis or allergic rhinitis. Due to this same vasoconstrictor effect also is decreased the nasal fluid production (since the distended vessels release liquid to nostrils (watery discharge of the common cold)4-6.        Therefore, It is used to relieve nasal congestion and excess mucus fluid, not to alleviate cough.        For ipratropium bromide, it has been traditionally used as a bronchodilator in asthma and chronic obstructive pulmonary disease, being its main use by micronebulizator7-9 or by oral metered dose inhaled aerosol. More recently it has been experimentally used to reduce nasal secretion11,18.        